Influence of Resistance to Streptogramin A Type Antibiotics on the Activity of Quinupristin-Dalfopristin In Vitro and in Experimental Endocarditis Due

We evaluated the activity of quinupristin-dalfopristin (Q-D) against three clinical strains of Staphylococcus aureus susceptible to Q (MIC, 8 mg/ml) and Q-D (MICs, 0.5 to 1 mg/ml) but displaying various levels of sus-ceptibility to D. D was active against S. aureus HM 1054 (MIC, 4 mg/ml) and had reduced activity against S. aureus RP 13 and S. aureus N 95 (MICs, 32 and 64 mg/ml, respectively). In vitro, Q-D at a concentration two times the MIC (23MIC) produced reductions of 4.3, 3.9, and 5.8 log10 CFU/ml after 24 h of incubation for HM 1054, RP 13, and N 95, respectively. Comparable killing was obtained at 83MIC. Q-D-resistant mutants were selected in vitro at a frequency of 2 3 1028 to 2 3 1027 for the three strains on agar containing 23MIC of Q-D; no resistant bacteria were detected at 43MIC. Rabbits with aortic endocarditis were treated for 4 days with Q-D at 30 mg/kg of body weight intramuscularly (i.m.) three times a day (t.i.d.) or vancomycin at 50 mg/kg i.m. t.i.d. In vivo, Q-D and vancomycin were similarly active and bactericidal against the three tested strains compared to the results for control animals (P < 0.01). Among animals infected with RP 13 and treated with Q-D, one rabbit retained Q-D-resistant mutants that were resistant to Q and to high levels of D (MICs, 64,>256, and 8 mg/ml for Q, D, and Q-D, respectively). We conclude that the bactericidal activity of Q-D against strains with reduced susceptibility to D and susceptible to Q-D is retained and is comparable to that o